Is CTAGE9 p.Ala208Val (c.623C>T) pathogenic?

CTAGE9 p.Ala208Val (c.623C>T) is classified Uncertain significance in CTAGE9 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-28). AlphaMissense: likely benign (0.1692); Very rare (popmax 0.00723%, afr).

How common is CTAGE9 p.Ala208Val (c.623C>T) in the general population?

CTAGE9 p.Ala208Val (c.623C>T) is very rare (popmax 0.00723%, afr) (gnomAD).

What do computational predictors say about CTAGE9 p.Ala208Val (c.623C>T)?

AlphaMissense predicts likely benign (score 0.1692) — an in-silico prediction, not a clinical call.

CTAGE9 p.Ala208Val

c.623C>T · rs986463275 · VCV2259356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1692 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00723%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1692	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.67	GERP 0.96
Regional constraint	o/e 0.03	constrained · MANE · 294 bp · p 9.7e-25 · regional, not allelic
Overall
CADD	12.09	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00723% African / African-American · 5/69,152 alleles

Filtering AF 0.00281% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0021%

Overall 0.00275% 42/1,529,616 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00723%	13,830
European (non-Finnish)	0.00326%	30,698

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CTAGE9
Protein: p.Ala208Val
Coding: c.623C>T
MANE Select: NM_001145659
dbSNP: rs986463275
Type: single nucleotide variant
Location: chr6:131710395 (GRCh38)
Gene constraint: LOEUF 1.713 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 69.37

Full CTAGE9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTAGE9 p.Ala120Thr Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala120Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala122Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala168Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala280Val Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala321Thr Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala48Pro Uncertain significance ★ ⚠ same type
CTAGE9 p.Ala748Val Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ctage9-p-ala208val (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown